1. Field of the Invention
This invention deals generally with diagnostic methods for determining the condition of bones. In particular, it discloses a method for non-invasively, in vivo, determining the condition of certain bones in humans and animals. This information can be used to evaluate whether or not the subject has any disorders relating to variations in bone condition, such as osteoporosis (abnormally low bone density) or osteopetrosis (abnormally high bone density).
2. Discussion of the Problem and Objects of the Invention
This invention pertains to detecting bone disease and other abnormal bone conditions. The invention is intended specifically for evaluation and diagnosis of humans, but with obvious modification of the illustrative embodiments, the invention could be used to evaluate animal bones, also. The main object is to diagnose the presence of osteoporosis. However, other conditions may also be detected using this method, including bone condition variations following renal failure and periodontal disease due to bone deterioration The invention may also be useful both for detecting fractures and for assessing, quantitatively, the healing of fractures.
The human skeleton is composed of tubular (long and hard) and cancellous (spongy) bones, each of which is composed of, specific proportions of cortex (compact bone) and trabeculae (connective strands). Tubular bones, which are composed largely of cortex, dominate the appendicular skeleton that makes up the limbs; cancellous bones, which are composed primarily of trabecular bone, dominate the axial skeleton of the vertebral column and pelvis.
In both cortical and trabecular bone, the collagen fibrils extend throughout. The difference between the two is actually one of degree, depending upon the form the network of collagen fibrils takes. In general, the fibrils may be separated such that the network is a network of rods. They may also be more closely spread, so that the network appears as a network of plates connected by rods. In both cases, a certain volume of the bone will comprise mineralized collagen fibrils, and a certain volume will comprise fluid known as "marrow."
Whether or not a particular bone assumes a trabecular or cortical formation is thought to depend largely upon the function that bone serves. The method of bone formation is not well understood; however, it is believed that the process of bone accretion responds in some manner to stresses experienced by the bone. Therefore, that region of a bone that experiences relatively high stresses, such as the diaphysis of the tibia of the leg, tends more toward cortical bone Regions of a bone that experience low stress tend more to be trabecular. In most sites of trabecular bone, the trabecular mass is surrounded by a relatively thin layer of cortical bone The patella (kneecap) is mostly trabecular with a subcortical layer just beneath the anterior surface.
The principal target of the invention, osteoporosis, is a disease of unknown cause which afflicts people, generally, as they age. Osteoporosis afflicts women more often than men, and of women, more often after menopause. White women are more often stricken than women of other races Osteoporosis is manifest as an absolute decrease in bone tissue mass. The bone that remains is, however, normal A person suffering from osteoporosis loses a greater proportional amount of trabecular bone than cortical bone Common manifestations of osteoporosis are a hunched back, caused by crush fractures of the vertebrae, and fractures of the neck, the femur (upper thigh bone) and distal end of the radius (wrist bone).
Osteoporosis is a particularly insidious condition, because during its early phases physical deformity is not evident. Because osteoporosis develops progressively, early diagnosis and appropriate treatment may turn an otherwise serious onslaught Additionally, because of the mode by which bone is formed, an enhanced exercise regimen during the patient's younger years, coupled with an appropriate diet, has been thought to also minimize the effects of the condition. With women, it is appropriate to begin these programs prior to menopause. The diagnosis and treatment of osteoporosis is complicated by the fact that every patient has a different "normal" bone density; thus it is beneficial to generate a historical record of the changes in some property of the individual patient's bones (i.e., density or elasticity) and to make a diagnosis, at least in part, on the basis of historical trends.
Another target of the invention, periodontal disease, involves loss of bone in the mandible and maxilla, with consequential loosening of teeth. Heretofore, the progress of bone loss in the jaw has been monitored with X-rays, which can only reveal the presence of periodontal disease after substantial bone loss has already occurred.
Consequently, it is highly desirable to provide a means for detecting changes of bone condition (including, but not limited to the loss of bone material and attendant decrease in bone density and elasticity). Optimally, such means is non-invasive, accurate, sensitive, easy to use and can be made generally available. This is not, however, true of the prior art techniques, in general.
Recently, several methods have been proposed for the early diagnosis of osteoporosis. These methods include Neutron Activation Analysis of Total Body Calcium (TBC), single photon absorptiometry (of the wrist and oscalcus) and dual photon absorptiometry (of the spine and neck of the femur), Computer Aided Tomography (CAT scanning) and methods of ultrasound analysis.
The TBC method, briefly described, is as follows: TBC requires a source of fast neutrons, having energy of approximately 14 MeV. A beam of neutrons is directed at the subject. Depending upon the energy of the incident neutron beam, the nuclei of certain atoms capture the neutrons and become excited. The excited isotopes revert to a stable condition by emitting one or more gamma rays, either immediately (on the order of 10-12 seconds) or after a decay period characteristic of the activation product. The energy of the emitted gamma ray characterizes the target element. Calcium emits gamma rays at an energy of 3.1 MeV. The intensity of the gamma rays, i.e., a count rate per unit volume, indicates the amount of the subject element present. A disadvantage of TBC is that it convenienty measures only the total body calcium, thus, localized change in bone mass, as may be present in early stages of osteoporosis, will not be discernible. Further, TBC facilities require a neutron source, such as a nuclear reactor, a cyclotron or a radioactive material. They also include a large and sophisticated machine, and thus are relatively expensive, and rare. Thus, they are not available for most patients. As can be expected, this method is relatively expensive. Finally, a large radioactive dose of 0.3-0.5 rem is required, inhibiting repeat testing.
Photon absorptiometry is a technique that depends upon the absorption by a material, of discreet energy photons. In single photon absorptiometry, a single energy source emits a beam of monochromatic photons. The intensity of transmitted photons attenuates exponentially with respect to the mass of the substance in the path of the photons. Knowing the distance travelled, the density of the intervening substance can be determined. The problem with single energy photon devices is that they cannot resolve the effect of multiple attenuating layers, such as soft tissue surrounding bone.
Thus, dual photon absorptiometry is used According to this method, a single source having photons of two discreet energies, such as .sup.153 Gd, or two discreet energy sources such as .sup.125 I and .sup.241 Am are used. Two equations, each in two unknowns, result, relating the unattenuated and the attenuated photon intensities to the densities of the two substances. The two equations can be solved, and the two densities can be determined As is the case with respect to TBC, the equipment is relatively expensive and rare. Further, because soft tissue is made up of different components of skin, fat and muscle, a "fat/lean" adjustment factor must be used.
Density of bones can also be determined by using a CAT scan. A CAT scanner is a device which computes an image from multiple incidents of X-ray transmission. The patient is placed in a hollow cyclinder having X-ray sensitive receivers around the entire circumference. An X-ray source revolves around the patient, sending individual beams of X-rays through the patient to be received by the receiver at the opposite end of a diameter of the cylinder. This transmission is repeated for the entire circumference of the cylinder. The intensity of X-rays received by the receiving sensor is related to the total density of the path through the patient's body. A large number of these readings are taken as the transmitter circumnavigates the patient Sophisticated computerized analysis collates the readings received at each receiver, and generates a map of the density of a thin slice of the patient's body taken parallel to the plane defined by the many transmitted beams.
The output of the CAT scan is a density map. A CAT scan through bony areas will provide information relative to the density of the bones. The asserted advantages of the CAT scan are that it is a reproducible and reliable device, that it has been well tested in other related fields. Further, it quantifies the trabecular and cortical density separately. Thus, the exact density of the cancellous bone may be determined, without any averaging effect caused by the presence of the surrounding compact cortical bone.
Drawbacks to the CAT scanning technique are that the equipment is expensive and that it is not available in many communities. Further, it is not portable and may be regarded as traumatic for certain patients. Administration of CAT scans must be done by licensed doctors of radiology or technicians associated with radiologists, thereby further increasing the cost. Finally, CAT scans involve X-ray exposure to the patient, which is seen as undesirable by some doctors and patients. "Patient", as used herein, refers to both human and animal subjects.
For in vivo, non-invasive analysis of bones in humans and other animals, measurement by use of ultrasound also has been performed. Such measurement is complicated, though, by the presence of soft tissue surrounding most bones. The speed of an ultrasound signal injected transdermally is affected by passage through the soft tissue surrounding the bones, as well as by passage through the bone(s) of interest It is possible to minimize the effect of the soft tissue; however, prior attempts to do so have been encumbered by requirements for rather sophisticated echo analysis and careful measurement. See, for example, U.S. Pat. No. 4,361,154, "Method for Establishing, In Vivo, Bone Strength."
Thus, the several objects of this invention are: (1) to evaluate bone condition in patients with a non-invasive, in vivo technique; (2) to evaluate bone condition without subjecting patients to substantial doses of X-rays; (3) to evaluate bone condition in patients economically and quickly; (4) to provide a method or methods of evaluating bone condition that may be performed safely and economically many times over the course of several years; and (5) to provide a method or methods of evaluating bone condition that may be performed by a technician without the need for expensive equipment, especially careful measurement or complex analysis.
As used herein, "patella" refers to the thick, flat triangular bone that forms the anterior part of the knee; "kneecap" refers to the patella and surrounding soft tissue; "tibia" refers to the anterior bone of the lower leg; "shin" refers to the tibia and surrounding soft tissue.